Interest continues in finding faster and less expensive ways for sequencing DNA. One of the approaches under study in several laboratories is to form dideoxy sequencing ladders and measure them by mass spectrometry. Some success has been achieved in measuring short ladders by MALDI-MS, but not long ladders, so the latter are being sequenced by electrophoresis. Unfortunately, electrophoresis for this purpose is a slow and expensive technique. At least in part, the tendency of the DNA molecule to fragment, depurinate and form adduct ions in MALDI-MS has limited the performance of this method. In this proposal, a novel technique is presented which potentially may overcome these problems, and thereby advance the usefulness of mass spectrometry for the measurement of dideoxy DNA sequencing ladders.